Skip to main content Accessibility help
  • Cited by 1
  • Print publication year: 2012
  • Online publication date: August 2012

14 - Controversial findings on the role of NMDA receptors in traumatic brain injury

from Section 1 - Traumatic Brain Injury


1. Paoletti P , Neyton J . NMDA receptor subunits: function and pharmacology. Curr Opin Pharmacol 2007;7:39–47.
2. Kalia LV , Kalia SK , Salter MW . NMDA receptors in clinical neurology: excitatory times ahead. Lancet Neurol 2008;7:742–55.
3. Salter MW , Kalia LV . Src kinases: a hub for NMDA receptor regulation. Nat Rev Neurosci 2004;45:317–28.
4. Benveniste H , Drejer J , Schousboe A , et al. Elevation of extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J. Neurochem 1984;43:1369–74.
5. Obrenovitch TP , Urenjak J , Zilkha E , et al. Excitotoxicity in neurological disorders–the glutamate paradox. Int J Dev Neurosci 2000;18:281–87.
6. Meldrum BS . Protection against neuronal damage by drugs acting on excitatory neurotransmission. Cerebrovasc Brain Metabol Rev 1990;2:27–57.
7. Choi DW . NMDA receptors and AMPA/kainate receptors mediate parallel injury in cerebral cortical cultures subjected to oxygen-glucose deprivation. In Kogure K, Hossmann K-A, Siesjo BK, eds. Progress in Brain Research vol. 96. Amsterdam: Elsevier; 1993. pp. 137–43.
8. Faden AI , Demediuk P , Panter SS , et al. The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 1989;244:798–800.
9. Nilsson P , Hillered L , Ponten U , et al. Changes in cortical extracellular levels of energy-related metabolites and amino acids following concussive brain injury in rats. J Cereb Blood Flow Metab 1990;10:631–37.
10. Bullock R , Zauner A , Woodward JJ , et al. Factors affecting excitatory amino acid release following severe human head injury. J Neurosurg 1998;89:507–18.
11. Palmer AM , Marion DW , Botscheller ML , et al. Traumatic brain injury-induced excitotoxicity assessed in a controlled cortical impact model. J Neurochem 1993;61:2015–24.
12. Davalos A , Castillo J Serena J , et al. Duration of glutamate release after acute ischemic stroke. Stroke 1997;28:708–10.
13. Hayes RL , Jenkins LW , Lyeth BG , et al. Pretreatment with phencyclidine, an N-methyl-D-aspartate antagonist, attenuates long-term behavioral deficits in the rat produced by traumatic brain injury. J Neurotrauma 1988;5:259–74.
14. McIntosh TK , Vink R , Soares H , et al. Effects of the N-methyl-D-aspartate receptor blocker MK-801 on neurologic function after experimental brain injury. J Neurotrauma 1989;6:247–59.
15. Shapira Y , Yadid G , Cotev S , et al. Protective effect of MK801 in experimental brain injury. J Neurotrauma 1990;7:131–99.
16. Bernert H , Turski L . Traumatic brain damage prevented by the non-N-methyl-D-aspartate antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo[f] quinoxaline. Proc Natl Acad Sci USA 1996;93:5235–40.
17. Kroppenstedt SN , Schneider GH , Thomale UW , et al. Protective effects of aptiganel HCl (Cerestat) following controlled cortical impact injury in the rat. J Neurotrauma 1998;15:191–97.
18. Okiyama K , Smith DH , White WF , et al. Effects of the novel NMDA antagonists CP-98,113, CP-101,581 and CP-101,606 on cognitive function and regional cerebral edema following experimental brain injury in the rat. J Neurotrauma 1997;14 :211–22.
19. Okiyama K , Smith DH , White WF , et al. Effects of the NMDA antagonist CP-98,113 on regional cerebral edema and cardiovascular, cognitive, and neurobehavioral function following experimental brain injury in the rat. Brain Res 1998;792:291–8.
20. Willis C , Lybrand S , Bellamy N . Excitatory amino acid inhibitors for traumatic brain injury. Cochrane Database Syst Rev 2004;1.
21. Narayan RK , Michel ME , Ansell B , et al. Clinical trials in head injury. J Neurotrauma 2002;19:503–57.
22. Beauchamp K , Mutlak H , Smith WR , et al. Pharmacology of traumatic brain injury - where is the “golden bullet”? Mol Med 2008;14:731–40.
23. Morris GF , Bullock R , Marshall SB , et al. Failure of the competitive N-methyl-D-aspartate antagonist Selfotel (CGS 19755) in the treatment of severe head injury: results of two phase III clinical trials. The Selfotel Investigators. J Neurosurg 1999;91:737–43.
24. Merchant RE , Bullock MR , Carmack CA , et al. A double-blind, placebo-controlled study of the safety, tolerability and pharmacokinetics of CP-101,606 in patients with a mild or moderate traumatic brain injury. Ann N Y Acad Sci 1999; 890:42–50.
25. Yurkewicz L , Weaver J , Bullock MR , et al. The effect of the selective NMDA receptor antagonist traxoprodil in the treatment of traumatic brain injury. J Neurotrauma 2005;22:1428–43.
26. Barth TM , Grant ML , Schallert T . Effect of MK801 on recovery from sensorimotor cortex lesion. Stroke 1990;11:153–57.
27. Ikonomidou C , Stefovska V , Turski L . Neuronal death enhanced by N-methyl-D-aspartate antagonists. Proc Natl Acad Sci USA 2000;97:12885–90.
28. Moratalla R , Barth TM , Bowery NG . Benodiazepine receptor autoradiography in corpus striatum of rat after large frontal cortex lesions and chronic treatment with diazepam. Neuropharmacology 1989;28:893–900.
29. Dietrich WD , Alonso O , Busto R , et al. Influence of amphetamine treatment on somatosensory function of the normal and infracted rat brain. Stroke 1990;21:147–50.
30. Hornstein A , Lennihan L , Seliger G , et al. Amphetamine in recovery from brain injury. Brain Injury 1996;10:145–48.
31. Biegon A , Fry PA , Paden CM , et al. Delayed activation, rather than inhibition, of glutamate NMDA receptors improves neurological outcome after closed head injury in mice. Proc Natl Acad Sci USA 2004;101:5117–22.
32. Temple MD , Hamm RJ . Chronic, post-injury administration of D-cycloserine, an NMDA partial agonist, enhances cognitive performance following experimental brain injury. Brain Res 1996;741:246–51.
33. Heifets LB. Antimycobacterial drugs. Semin Respir Infect 1994;9:84–103.
34. Yaka R , Biegon A , Grigoriadis N , et al. D-cycloserine improves functional recovery and reinstates long-term potentiation (LTP) in a mouse model of closed head injury. FASEB J 2007;21:2033–41.
35. Adeleye A , Shohami E , Nachman D , et al. D-cycloserine improves functional outcome after traumatic brain injury with wide therapeutic window. Eur J Pharmacol 2010;629:25–30.
36. Miller LP , Lyeth BG , Jenkins LW , et al. Excitatory amino acid receptor subtype binding following traumatic brain injury. Brain Res 1990;526:103–7.
37. Sihver S , Marklund N , Hillered L , et al. Changes in mACh, NMDA and GABA(A) receptor binding after lateral fluid-percussion injury: in vitro autoradiography of rat brain frozen sections. J Neurochem 2001;78:417–23.
38. Grossman R , Shohami E , Alexandrovich A , et al. Increase in peripheral benzodiazepine receptors and loss of glutamate NMDA receptors in a mouse model of closed head injury: a quantitative autoradiographic study. Neuroimage 2003;20:1971–81.
39. Malenka RC , Nicoll RA . Long-term potentiation – a decade of progress? Science 1999;285:1870–74.
40. Schumann J , Alexandrovich AG , Biegon A , et al. Inhibition of NR2B phosphorylation restores alterations in NMDA receptor expression and improves functional recovery following traumatic brain injury in mice. J Neurotrauma 2008;25:945–57.
41. Giza CC , Maria NS , Hovda DA . N-Methyl-D-aspartate receptor subunit changes after traumatic injury to the developing brain. J Neurotrauma 2006;23:950–61.
42. Bergsneider M , Hovda DA , McArthur DL , et al. Metabolic recovery following human traumatic brain injury based on FDG-PET: time course and relationship to neurological disability. J Head Trauma Rehabil 2001;16:135–48.
43. Yoshino A , Hovda DA , Kawamata T , et al. Dynamic changes in local cerebral glucose utilization following cerebral contusion in rats: evidence of a hyper- and subsequent hypometabolic state. Brain Res 1991;561:106–19.
44. Dhawan J , Benveniste H , Nawrocky M , et al. Transient focal ischemia results in persistent and widespread neuroinflammation and loss of glutamate NMDA receptors. Neuroimage 2010;51:599–605.
45. Biegon A , Alvarado M , Budinger TF , et al. Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain. J Neurochem 2002;82:924–34.
46. Rod MR , Auer RN . Pre- and post-ischemic administration of dizocilpine (MK-801) reduces cerebral necrosis in the rat. Can J Neurol Sci 1989;16:340–4.
47. Hoyte L , Barber PA , Buchan AM , et al. The rise and fall of NMDA antagonists for ischemic stroke. Curr Mol Med 2004;4:131–36.
48. Ikonomidou C , Turski L . Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol 2002;1:383–86.
49. Sanders MJ , Sick TJ , Perez-Pinzon MA , et al. Chronic failure in the maintenance of long-term potentiation following fluid percussion injury in the rat. Brain Res 2000;861:69–76.
50. Cao R , Hasuo H , Ooba S . et al. Facilitation of glutamatergic synaptic transmission in hippocampal CA1 area of rats with traumatic brain injury. Neurosci Lett 2006;401:136–41.